Thoughts About My Career in the Field
Anat Stemmer-Rachamimov, MD
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Neurofibromatosis research and clinical work have been the center of my career for the past 30 years. It is difficult to remember how it all started…
I was a new postdoc in the laboratory of Dr. David Louis, in Massachusetts General Hospital (Boston; 1996-2000). The grant I was supposed to work on was not funded (a glioma grant). So, until we resubmit or come up with another grant, I was asked to help with the work relating to NF. This was a collaborative effort with Vijaya Ramesh, who also had a lab in the same floor. We were working on merlin, the NF2 protein, trying to understand its expression pattern in normal tissues (brain) and tumors (NF2-associated and sporadic). These early days were my introduction to the field and it was centered around mutation analysis, biochemistry (protein interactions) and correlations between mutations and protein expression in different NF2 associated tumor types. I was introduced to cell culture (which I found fascinating) and by the end of that year I was already very interested in NF.
My mentors in those early years were Vijaya Ramesh and Mia Maccollin. Mia, the director of the NF clinic in MGH at the time, had an infectious passion for NF and research. Her research was mostly focused on mutation analysis and genotype-phenotype correlations. I was fascinated by Mia not only because of her work in research but also because we shared a deep love for animals (especially dogs) and training. Mia was the link for me between the clinical world of NF and the basic science world, but her strength (sequencing and genetics) was not my niche. I found my niche in working on clinical pathological correlations – relating pathology and histological findings to basic science on the one hand and to clinical phenotype on the other.
My first grant was a DOD grant. It was a study of NF2 gene alteration in Schwannomas and Schwann cell tumorlets in NF2 patients. The assumption was the tumorlets are not neoplastic because they do not grow. However, our analysis showed that NF2 loss occurred in tumorlets. So the biological difference between tumorlets and schwannomas was not due to the NF2 gene loss, but to other factors…
In those early years, much of my work (mostly collaborative) was centered around understanding and documenting the NF2 alterations (germline and sporadic). Memories of that time revolve around many sequencing gels and western blots…
As time progressed, my work evolved to the pathological analysis of mouse models of neurofibromatoses. Collaborative work with the giants in the field: Marco Giovannini (nf2 mouse; schwannomas), Nancy Ratner (nf1 mouse models) and Michel Kalamarides (nf2 mice; meningiomas) was intense and fascinating. We published our findings, participated in consensus conferences, and laid down the preclinical work that finally led to the next research phase: the phase of treatment of the manifestations of NF.
The last phase, the one we are currently in, is mostly evolving around treatment, drug discovery, trials and attempts in formalizing clear categories in diagnosis and in treatment for all the different forms of NF. We are finally at the stage of meaningful treatment attempts based on the acquired knowledge of biology done in the past years. My collaboration in that last phase with neuro oncologists in the NF clinic: Scott Plotkin (director of NF clinic in MGH) and Justin Jordan and were often focused on clinical manifestations or treatment results/effects on tissues. In the basic science side, collaboration on treatment (including gene therapy) in multiple projects with Xandra Breakfield, Hiro Wakimoto, Sam Rabkin and Gary Brenner opened new possibilities and posed new challenges.
Our yearly meetings, organized by the Children Tumor Foundation, and other conferences organized by NTAP and by REINS, bring together the NF researchers and clinicians to exchange findings, form and foster new relationships. This is a chance to catch up with what is happening in the NF world in other places, in the US and in the world. International relationships are formed and exchanges of opinions, discussions and arguments. The engines behind these meetings; Annette Bekker, Jaishry Blakeley and Scot Plotkin, are the power that moves things forward faster.
My interest in NF is as strong (actually stronger) now than it was 30 years ago when I started on this path as a postdoc. I am still fascinated by the manifestations of the different forms of NF, by the complexity of the lesions, the challenges in diagnosis and the challenges in treatment. I am very grateful to my colleagues and collaborators, who made this a rewarding and wonderful journey. I have met so many wonderful, insightful, inspiring people, who share this passion with me, and over the years, friendships and bonds were formed that are very special and dear to my heart. It was a good decision to go into the NF research world, and if I would do it all over again.
